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Can exercise improve the effect of immune checkpoint inhibitors for cancer therapy?

A 2019/2020 Summer Studentship research project

Although immune checkpoint inhibitors can be remarkably effective, most patients will not have long-term responses. Efforts thus far to improve their efficacy have involved the combination with other cancer therapies such as chemotherapy and other immunotherapies. Although these combination strategies have improved treatment response, they are also associated with increased rates of severe toxicities leading to treatment cessation. Exercise is safe and may even reduce treatment-related side effects. This project comprises part of a larger study which is the first in the world to combine post-diagnosis exercise with immune checkpoint inhibitors. This study will provide valuable data on the use of exercise in combination with checkpoint inhibitors.

Student: Thomas Williams
Supervisors: Dr Abel Ang,  Linda Buss, Associate Professor Gabi Dachs
Sponsor: Cancer Society Diamond Harbour, Kaikoura & Rangiora Groups

Background

Exercise is known to positively influence immunity. Acute exercise mobilises lymphocytes to the bloodstream, and after the cessation of exercise, blood lymphocyte levels often drop below baseline. This is thought to be due to a redistribution of immune cells to peripheral tissues, including tumours, which may help the immune system to recognise and fight the tumour.

Immune checkpoint inhibitors are a relatively new class of anti-cancer drug designed to reactivate the host immune system to eliminate the tumour. In a small subset of patients they are remarkably effective, resulting in long-term responses, but the majority of patients will either present with primary resistance or develop resistance. There is significant interest internationally to improve the proportion of these long-term responses.

The tumour microenvironment consists both of tumour cells and other cell types such as vascular cells and immune cells. These additional cell types play a major role in determining how aggressively a tumour grows. Both exercise and immune checkpoint inhibitors can change aspects of the tumour microenvironment such as vascularity and immune cell infiltrate.

Aim

To determine the effect of concurrent exercise with cancer immune checkpoint inhibitor treatment by measuring changes in the tumour microenvironment and peripheral tissues.

Method

All tumour and tissue samples from exercising or non-exercising mice, treated or untreated with checkpoint inhibitor, are available for this laboratory study. Immunohistochemistry and/or Western blot analysis will be used to analyse protein levels of specific tumour and tissue components, such as tumour cell proliferation, immune cell infiltration, muscle exercise markers and signs of toxicity in internal organs.

Student researcher’s component of the study

The student will use immunohistochemistry and/or Western blotting techniques to investigate protein markers of tumour aggression, mouse fitness and signs of toxicity. The student will have the opportunity to perform all aspects of this process: tissue sectioning, immunostaining and imaging, as well as tissue lysing, PAGE electrophoresis and Western blot analysis. They will not be involved in animal work.

Student Prerequisites

Previous lab experience preferred, but the most important things are enthusiasm and attention to detail!

How to apply

Email abel.ang@otago.ac.nz